Throughout
humanity’s history, few things have seemed as random
as the onset of disease. What
makes Alzheimer’s bedevil your father,
while skipping you? Why are women seven times more likely to
get thyroid-crippling Grave’s disease than men? Are one’s
odds of getting colon cancer simply the luck of the draw? Preordained?
Somewhere in between? Thankfully, we live in an age
where medical researchers are increasingly finding the answers
to these questions are embedded in our genes. And the Miller
School of Medicine is poised to make a big difference, thanks
to the addition of a world-renowned husband-and-wife genetics
team. Margaret Pericak-Vance, Ph.D., and Jeffery Vance,
M.D., Ph.D., opened the Miller School’s Miami Institute
for Human Genomics (MIHG) in January, after more than two decades
of groundbreaking human genetics research at Duke University.
The Vances were enticed by Miller School Dean Pascal J. Goldschmidt,
M.D., who was previously chairman of Duke’s Department
of Medicine. It also didn’t hurt that UM President
Donna E. Shalala joined Goldschmidt in a tag-team effort to
lure the Vances to South Florida. “There’s
great leadership here in Donna Shalala and Pascal -Goldschmidt,” Vance
says from his sixth-floor office in the Clinical Research Building. “Of
course we knew Pascal well, so that was strong motivation.” The
drumbeat of genetics discoveries associated with the Vances
hasn’t slowed since their arrival at UM. In July, for
the first time in more than three decades, a multi-center
team of researchers, co-led by Pericak-Vance, announced they
had
uncovered a gene linked to multiple sclerosis (MS) on the
interleukin 7 receptor (IL7R) alpha chain gene. The findings
were published
in the journal Nature Genetics.

“This is the first MS-associated gene outside of the major
histocompatibility complex that has been confirmed in multiple
populations,” says
Pericak-Vance about the finding. “We took a very systematic
approach, we looked at multiple lines of evidence that would
give us the best chances of successfully identifying a gene that
was truly involved in MS susceptibility.”

A paper released simultaneously in The New
England Journal of Medicine (NEJM) confirmed the findings in the Nature
Genetics article. Pericak-Vance was also an author on the study in the NEJM. The finding could pave the way for future research and
treatment options for patients who suffer from the chronic
inflammatory disease of the central nervous system.

In April Vance and a team of genetic researchers
helped identify a key gene that could play a major role in
early-onset cardiovascular
disease in men under 51 and women under 56. Previous research
had identified a big area on chromosome three believed to be
important in cardiovascular disease, so the research focused
on a peak area of that chromosome in a genetic association
study. The strongest associations were found in three single
nucleotide
polymorphisms from the kalirin (KALRN) gene. The findings appeared
in The American Journal of Human Genetics.

“These findings open up a whole new area of study for looking
at risks of cardiovascular disease,” Vance says. “By
using the recent advances in genetic technology, you can find
things you never had any clue might be important.”

Given the Vances’ medical and scientific prowess, it shouldn’t
be long before UM is mentioned in the same breath as the Broad
Institute, a human genetics research institution in Cambridge,
Massachusetts.

What makes facilities like Broad stand out “is the quality
of the discoveries made at those places,” says Alan Packer,
senior editor of Nature Genetics. “Not only do they produce
high-impact research that everyone in the field has to stand
up and take notice of, but they have high-quality people, and
they’re successful at competing for grant money and putting
it to good use.

“The Vances have been authors of some very important discoveries,” Packer
observes. “They’re leaders in the field of human
genetics, and I’d imagine they’d bring quite a bit
of excitement to the University of Miami, as well as resources.”

At Duke the Vances did benchmark work that uncovered
the genetic footprints of a host of maladies, including cardiovascular
disease,
multiple sclerosis, autism, Alzheimer’s, and age-related
macular degeneration.

“Here at the institute our focus is on
identifying the genetic contributions to common diseases that
affect all of us,” Vance
says. “In the past, human geneticists worked with relatively
rare disorders that could be triggered if a single gene was
affected.

“Now we’re looking at susceptibility genes, which
are genes that make you more susceptible to common things like
Parkinson’s
and hypertension,” Vance continues. “They do this
in concert with other genes, as well as your environment.”

When the Vances left Duke, more than 50 of their
200 colleagues decided to pull up stakes and come to Miami.
In addition, $34
million in federal research grant money followed the Vances
and their colleagues.

To get the Miami Institute for Human Genomics
percolating at top speed, the Vances need even more funding
and manpower. MIHG
is currently authorized to fill 50 job openings.

“We need people who are molecular geneticists,
like myself, as well as clinicians, statistical geneticists,
programmers and
database people,” Vance says. Once that batch of staffers
is in place, MIHG will be looking to hire dozens more scientists
and staffers, according to Pericak-Vance, who is a genetic
epidemiologist.

Both have the ability to talk about their complex
work sans technical jargon. The Florida legislature understands
the potential impact
clearly, appropritating $80 million to support MIHG earlier
this year.

This is an impressive start, but one that must
be built upon, says Goldschmidt. “To attract even more top-notch researchers,
we are seeking additional funds,” adds Goldschmidt, who
anticipates that MIHG will trigger a South Florida biotech boom.

That’s not outside the realm of possibility, observes Sena
Black of Enterprise Florida, a statewide economic development
agency. “Right now I think South Florida is particularly
strong from a biotech standpoint, and I think genomics will make
it that much stronger,” she says. “An institute like
the Miami Institute for Human Genomics will really ensure that
Florida leads the way in health care delivery, new therapies,
and new ways of curing diseases.”

Regarding MIHG’s operations, Pericak-Vance
says her husband will be overseeing the laboratory side of
the equation. “I like the administrative stuff,” Pericak-Vance
says. “I like putting things together.”

There will certainly be plenty of lab and administrative
work to go around, because in addition to shepherding the institute
and its staff, the Vances are tasked
with starting a university-wide program in genetics, as well as a Ph.D. program
in the subject.

While the Vances are acclaimed scientists, if
you want to see Jeffery smile call him an “artiste.” That happens to be how he, his wife, and their
highly collaborative research team view themselves.

“If you think of creativity . . . science is very creative, which is why
people
like research,” he says, smiling. “Once you get into research, you’re
going where no one has gone before. That’s really exciting and calls for
outside-the-box abilities.”

The institute has five centers that cluster
faculty into their areas of expertise. The mission of the Center
for Human Molecular Genetics is to take some of the
more sophisticated approaches in molecular genetics and apply them to humans.
The Center for Disease Models studies different organisms; the Center for Genome
Technology is charged with conducting large-scale genetics studies; the Center
for Genetic Epidemiology and Statistical Genetics is responsible for applied
analysis and the development of new statistical genetics methodology. The mission
of the Center for Genomic Medicine is to turn research developments into new
treatments and cures.

Several of the institute’s researchers work on UM’s South Campus,
where a biorepository facility is maintained. It contains frozen blood samples
as well as extracted DNA, skin, various kinds of human cells, and brain material
from autopsies. In about a year’s time, the biorepository employees will
move with the rest of the institute onto four floors of the Biomedical Research
Building now under construction on the Miller School campus.

The genetics era at the Miller School began
in earnest about half a decade ago. Its roots can be traced
to an acclaimed medical genetics program at Emory University
in Atlanta. Program director Louis J. Elsas, M.D., was recruited by President
Shalala and former Miller School Dean John Clarkson, M.D., to bring his expertise
to Miami.

Ending a 32-year career at Emory, Elsas came
to the medical campus in 2003, working with the Departments
of Pediatrics and Neurology. A gift of $12.5 million from
the Dr. John T. Macdonald Foundation enabled the creation of the Dr. John T.
Macdonald Foundation Center for Medical Genetics.

In conjunction with Tallahassee lawmakers, Elsas
and his staff have dramatically expanded statewide infant screenings
for inherited metabolic disorders. Florida
newborns now undergo genetic screening for 40 maladies. Another of his major
achievements at UM concerns perceptions. He’s helped the research and medical
community at UM/Jackson get comfortable with the predictive ability of genetics.

“We started teaching first-year students at the Miller School medical genetics,” says
Elsas, who did his residency training in medical genetics at Yale University. “We
also started a four-year path that allows medical students to major in medical
genetics.”

The arrival of the Vances has focused an even
brighter light on genetics at the Miller School, a development
that pleases Elsas. “This is exciting and
really laudable and something I’m very much in favor of,” he says.

The Vances are enthused that their work has
brought them to Miami, with its ethnic and racial diversity. “One of the unique features about Miami is it’s
probably what America’s going to look like in ten years,” Pericak-Vance
says. “If you do the type of research we do, it’s really important
to be aware of ethnic differences and to study the relevant populations so that
everyone can benefit from the results.”

The creativity and intellectual rigor that go
into their genetics research makes it gratifying for the Vances.
But their work has a special meaning for the couple,
in light of the sudden death of their beloved 14-year-old son, Jeffery Joseph
Vance, in 1998.

A healthy teenager, “J.J.” Vance’s death was linked to thrombosis,
unexplained blood clots that rapidly materialized throughout his body. The Vances
are devoting part of their research to determine which genes facilitate the onset
of thrombosis.

“It’s important for us to do something
meaningful with our lives,” Vance
says. “This makes us feel like we’re doing something with real
significance.